PROJECT SUMMARY Viruses are predicted to cause nearly one fifth of all human cancers. At the McArdle Laboratory for Cancer Research at University of Wisconsin-Madison, the research program of Dr. Paul F. Lambert seeks to understand how a particular group of viruses, called DNA tumor viruses, contribute to cancer. One of the most well-recognized DNA tumor viruses associated with human cancer is human papillomavirus (HPV), which causes cancers of the cervix, head and neck, anus, and skin. For over 25 years, Dr. Lambert?s laboratory has focused on studying the viral and cellular mechanisms involved in HPV-associated cancer development using animal models and specialized tissue culture techniques. The laboratory is now applying these technical approaches to study a recently identified DNA tumor virus, Merkel cell polyomavirus (MCPyV), and its role in a rare form of human skin cancer. As an Assistant Scientist in the Lambert research program, I am directing two main areas of research: 1) evaluating the role of HPV, the female hormone estrogen, and the microenvironment in cervical cancer development, and 2) studying the role of MCPyV in human cancer. These studies make use of my education and technical training in the DNA tumor virus field in order to address novel and vital scientific research goals. For example, understanding the way in which HPV interacts with and modifies the surrounding microenvironment to promote cancer development will have broad implications on current paradigms in the field. My efforts to establish in vivo models using primary human cervical cancer samples provide an unprecedented opportunity to understand the role of estrogen in human cervical cancer, as well as a platform to explore the utility of using anti-estrogen drugs as a cervical cancer treatment. Moreover, continuing studies with a murine model of MCPyV T antigen expression that I helped to develop and characterize will help address a longstanding query of how polyomaviruses are involved in human cancers. Aside from my scientific responsibilities and contributions, my training and mentorship duties within the Lambert laboratory help ensure its continued growth and success. In the following grant application, my scientific and leadership roles within the Lambert research program, as well as how these efforts ultimately support the advancement of our collective scientific objectives, will be described.